RNA transmission and expression from inert HIV candidate vaccine virus-like-particles
Doctoral Thesis
2008
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University of Cape Town
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Abstract
HIV-1 Gag virus-like-particles (VLPs) produced in various expression systems are potent stimulators of both cellular and humoral immune responses in animal models. The encapsidation of large concentrations of random cellular RNA species is known to accompany the assembly of HIV virus particles. This RNA plays a crucial role by serving as a molecular scaffold for the assembly of Gag structural proteins into particles. Non-pseudotyped VLPs that do not present any HIV envelope glycoproteins are regarded as inert particles as they contain no replicative nucleic acid and are presumed to be unable to deliver encapsidated RNA for expression in inoculated individuals. Live virus cellular entry studies have shown that non-pseudotyped Gag particles are destined for degradation in acidified vesicles subsequent to receptor independent cellular entry. In addition to host cell RNA incorporation, Gag VLPs produced in insect cell-based, baculovirus expression systems have been observed to incorporate the baculovirus-derived Gp64 envelope glycoprotein. Gp64 has been shown to be efficient at enabling the delivery and expression of genes from recombinant baculoviruses and other Gp64 pseudotyped live viruses in mammalian cell lines both in vivo and in vitro. This study, therefore, set out to establish for the first time whether inert, baculovirus-derived (Gp64 pseudotyped) Gag VLPs could mediate delivery and expression of randomly encapsidated RNAs in mammalian cell lines.
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Includes abstract.
Includes bibliographical references (leaves 136-158).
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Valley-Omar, Z. 2008. RNA transmission and expression from inert HIV candidate vaccine virus-like-particles. University of Cape Town.